This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The hair-cell tip link, an essential component of the mechanotransduction apparatus in the inner ear, has been proposed to be formed partly by cadherin- 23 (CDH23) which is involved in hereditary deafness and belongs to the cadherin superfamily of proteins. Calcium ions are required for cadherin- mediated adhesion and also for maintaining the integrity of the tip link. Hair cells have an elastic gating spring, but it is unclear whether tip links have the appropriate elasticity. Certain mutations in CDH23 cause deafness, but it is not known how. In order to investigate the molecular architecture and elasticity of the tip link and its deafness related mutants we aim to determine the x-ray crystallographic structures of key CDH23 domains involved on tip link assembly and deafness.